Schlaifer D, Meyer K, Muller C, Attal M, Smith M T, Tamaki S, Weimels J, Pris J, Jaffrézou J P, Laurent G
Hematology Department, CHU Purpan, Toulouse, France.
Leukemia. 1994 Feb;8(2):289-91.
Myeloperoxidase (MPO), a heme-peroxidase found in the HL-60 myeloblastic cell line, is involved in vincristine (VCR) metabolism and the inactivation of this drug. We have examined whether decreased MPO activity correlated with increased sensitivity to VCR toxicity in myeloid leukemia cells. We have used MPO antisense RNA to reduce 60% of the MPO activity in the HL-60 cells. The MPO-deficient HL-60 cell line, C15, was significantly more sensitive to VCR than the parental MPO-positive cell line. Both cell lines were negative for P170-glycoprotein expression. Conversely, an MPO-positive C15 subclone was more resistant to VCR than the MPO-deficient C15 cell line. No significant differences in cytotoxic effects were observed between MPO-positive and MPO-deficient cells, following treatment with either daunorubicin or actinomycin D, two multidrug resistance-related drugs. These results strongly support an important role for MPO in VCR resistance in HL-60 cells. Antisense manipulation of the MPO content of myeloid cells could be of potential interest in leukemia treatment.
髓过氧化物酶（MPO）是一种存在于HL-60髓母细胞系中的血红素过氧化物酶，参与长春新碱（VCR）的代谢及该药物的失活过程。我们研究了髓系白血病细胞中MPO活性降低是否与对VCR毒性的敏感性增加相关。我们使用MPO反义RNA使HL-60细胞中的MPO活性降低了60%。MPO缺陷的HL-60细胞系C15对VCR的敏感性明显高于亲代MPO阳性细胞系。两种细胞系的P170-糖蛋白表达均为阴性。相反，MPO阳性的C15亚克隆比MPO缺陷的C15细胞系对VCR更具抗性。在用柔红霉素或放线菌素D（两种与多药耐药相关的药物）处理后，MPO阳性和MPO缺陷细胞之间未观察到细胞毒性作用的显著差异。这些结果有力地支持了MPO在HL-60细胞对VCR耐药中起重要作用。对髓系细胞MPO含量进行反义操作在白血病治疗中可能具有潜在意义。
